Evaluation of the anti-RANKL monoclonal antibody in rheumatoid arthritis rats.

Objectives: In this study, we aimed to investigate the therapeutic effect of anti-receptor activator of nuclear factor kappa-κB ligand (RANKL) monoclonal antibodies R748-1-1-1, R748-1-1-2 and R748-1-1-3 on rheumatoid arthritis (RA) in a rat model. Materials and methods: Gene cloning, hybridoma technology, affinity purification, enzyme-linked immunosorbent assay, general observation, hematoxylin-eosin staining, X-ray, and many other experimental techniques were used in this study. Results: Improved collagen-induced arthritis (CIA) modeling was successfully constructed. The RANKL gene was cloned and the anti-RANKL monoclonal antibody was prepared. Following treatment with the anti-RANKL monoclonal antibody, the soft tissue swelling of the hind paws, the joint thickening, the narrowed joint gap, and the blurred edge of the bone joint were improved. The pathological changes such as synovial hyperplasia of fibrous tissue, cartilage and bone destruction were significantly decreased in the anti-RANKL monoclonal antibody-treated CIA group. Compared to the normal control group and phosphate buffer saline (PBS)-treated CIA group, the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) in antibody-treated CIA group, positive drug-treated CIA group, and IgG-treated CIA group were decreased (p<0.05). Conclusion: The anti-RANKL monoclonal antibody can promote the therapeutic effect of RA rats, indicating that the anti-RANKL monoclonal antibody has a certain potential value and may be beneficial to the further study of the mechanism of RA treatment.

Meta-analysis of the efficacy of combined Chinese and Western medical treatment versus western medical treatment alone on pit viper bites.

This paper uses Meta-analysis to explore the differences in the clinical efficacy of combined Chinese and Western medical treatment of pit viper bites versus Western medicine alone. By searching English databases (PubMed, Embase and Cochrane Library) and Chinese databases (CNKI, Wanfang and VIP), we collected original studies related to this problem. After data extraction, meta-analysis was performed using 5.2-0 in R language. In this study, a total of 7891 patients with pit viper bites were included in 9 studies. Combined Chinese and Western medicine treatment may be superior to Western medicine treatment alone with an OR of 5.30 and 95% CI of 3.90-7.21. The combined treatment of Chinese and Western medicine has better clinical results in the recovery of local symptoms in patients with pit viper bites and is more effective than conventional Western medicine alone.

Extracellular vesicles from Zika virus-infected cells display viral E protein that binds ZIKV-neutralizing antibodies to prevent infection enhancement.

Mosquito-borne flaviviruses including Zika virus (ZIKV) represent a public health problem in some parts of the world. Although ZIKV infection is predominantly asymptomatic or associated with mild symptoms, it can lead to neurological complications. ZIKV infection can also cause antibody-dependent enhancement (ADE) of infection with similar viruses, warranting further studies of virion assembly and the function of envelope (E) protein-specific antibodies. Although extracellular vesicles (EVs) from flavivirus-infected cells have been reported to transmit infection, this interpretation is challenged by difficulties in separating EVs from flavivirions due to their similar biochemical composition and biophysical properties. In the present study, a rigorous EV-virion separation method combining sequential ultracentrifugation and affinity capture was developed to study EVs from ZIKV-infected cells. We find that these EVs do not transmit infection, but EVs display abundant E proteins which have an antigenic landscape similar to that of virions carrying E. ZIKV E-coated EVs attenuate antibody-dependent enhancement mediated by ZIKV E-specific and DENV-cross-reactive antibodies in both cell culture and mouse models. We thus report an alternative route for Flavivirus E protein secretion. These results suggest that modulation of E protein release via virions and EVs may present a new approach to regulating flavivirus-host interactions.

A Meta-Analysis of the Effect of Exercise Rehabilitation Care on Cardiac Function in Patients with Chronic Heart Failure.

Aims: Effect of systematic exercise rehabilitation nursing on patients with chronic heart failure. Materials and Methods: From January 1, 2021, to March 22, 2006, a comprehensive search was conducted on China Knowledge Network (CNKI), Wanfang, VIPERS (VIP), China Biomedical Literature Database (CBM), PubMed, Cochrane Library, EMBASE library database, and clinical registry to obtain the literature on the impact of exercise rehabilitation nursing on cardiac function of patients with chronic heart failure. From January 1, 2006, to March 22, 2021, the literature of randomized controlled trials (RCTs) on the effect of exercise rehabilitation nursing on cardiac function in patients with chronic heart failure was collected. According to the inclusion and exclusion criteria, literature screening, data extraction, and quality evaluation were carried out. Cochrane system assessor manual version 5.0 was used for quality assessment, and Review Manager Version 5.3 was used for meta-analysis. Results: A total of 9 articles were included, including 752 patients. Meta-analysis showed that exercise rehabilitation nursing had a significant effect on cardiac function indexes (LVESV, LVEF, CRP, BNP, and LVEDV) in patients with chronic heart failure (P < 0.05). Conclusion: Exercise rehabilitation nursing has a good effect on improving cardiac function in patients with chronic heart failure. It can improve cardiac function indexes such as left ventricular end-systolic volume, right ventricular ejection fraction, brain natriuretic peptide, and left ventricular end-diastolic volume in patients with chronic heart failure.

Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion.

Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasdermin D (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309-313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation.

Change in the intestinal bacterial community structure associated with environmental microorganisms during the growth of Eriocheir sinensis.

As an important organ to maintain the host's homeostasis, intestinal microbes play an important role in development of the organism. In contrast to those of terrestrial animals, the intestinal microbes of aquatic organisms are affected by environmental microorganisms (including water microorganisms and sediment microorganisms). In the present study, the compositional differences of intestinal microbes in three representative developmental stages of the Chinese mitten crab (Eriocheir sinensis) were studied. Meanwhile, network association analysis, and visualization of the water microorganisms of the crabs' habitat, the environment microorganisms in the pond, and the intestinal microbes, was carried out. The results showed that the gut microbiota diversity index decreased continuously with age, and the four bacteria of Aeromonas (Proteobacteria), Defluviitaleaceae (Firmicutes), Candidatus Bacilloplasma (Tenericutes), and Dysgonomonas (Bacteroidetes) were the "indigenous" flora of the crab. In the network-related analysis with the environment, we found that as the culture time increased, the effect of environmental microorganisms on the intestinal microbes of crabs gradually decreased, and the four "indigenous" bacteria were always unaffected by the environmental microorganisms. The results of this study identified the core bacteria of the crab and, for the first time, studied the relationship between intestinal environmental microorganisms, which will aid the practical production of crabs and will promote research into the relationship between specific bacteria and the physiological metabolism of crabs.

HCV Reporter System (Viral Infection-Activated Split-Intein-Mediated Reporter System) for Testing Virus Cell-to-cell Transmission ex-vivo.

Hepatitis C virus (HCV) spread involves two distinct entry pathways: cell-free transmission and cell-to-cell transmission. Cell-to-cell transmission is not only an efficient way for viruses to spread but also an effective method for escaping neutralizing antibodies. We adapted the viral infection-activated split-intein-mediated reporter system (VISI) and developed a straightforward model for Live-cell monitoring of HCV cell-to-cell transmission ex-vivo: co-culture of HCV infected donor cells (red signal) with uninfected recipient cells (green signal) and elimination of the cell-free transmission by adding potent neutralizing antibody AR3A in the supernatant. With this model, the efficiency of cell-to-cell transmission can be evaluated by counting the number of foci designated by the green signal of recipient cells.

Visualizing the Essential Role of Complete Virion Assembly Machinery in Efficient Hepatitis C Virus Cell-to-Cell Transmission by a Viral Infection-Activated Split-Intein-Mediated Reporter System.

Hepatitis C virus (HCV) infects 2 to 3% of the world population and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. Many aspects of HCV study, ranging from molecular virology and antiviral drug development to drug resistance profiling, were supported by straightforward assays of HCV replication and infection. Among these assays, the HCV-dependent fluorescence relocalization (HDFR) system allowed live-cell visualization of infection without modifying the viral genome, but this strategy required careful recognition of the fluorescence relocalization pattern for its high fluorescence background in the cytoplasm. In this study, to achieve background-free visualization of HCV infection, a viral infection-activated split-intein-mediated reporter system (VISI) was devised. Uninfected Huh7.5.1-VISI cells show no background signal, while HCV infection specifically illuminates the nuclei of infected Huh7.5.1-VISI cells with either green fluorescent protein (GFP) or mCherry. Combining VISI-GFP and VISI-mCherry systems, we revisited HCV cell-to-cell transmission with clear-cut distinction of donor and recipient cells in a live-cell manner. Independently of virion assembly, exosomes have been reported to transfer HCV subgenomic RNA to initiate replication in uninfected cells, which suggested an assembly-free pathway. However, our data demonstrated that HCV structural genes and the p7 gene were essential for not only cell-free infectivity but also cell-to-cell transmission. Additionally, depletion of apolipoprotein E (ApoE) from donor cells but not from recipient cells significantly reduced HCV cell-to-cell transmission efficiency. In summary, we developed a background-free cell-based reporter system for convenient live-cell visualization of HCV infection, and our data indicate that complete HCV virion assembly machinery is essential for both cell-free and cell-to-cell transmission. IMPORTANCE: Hepatitis C virus (HCV) infects hepatocytes via two pathways: cell-free infection and cell-to-cell transmission. Structural modules of the HCV genome are required for production of infectious cell-free virions; however, the role of specific genes within the structural module in cell-to-cell transmission is not clearly defined. Our data demonstrate that deletion of core, E1E2, and p7 genes individually results in no HCV cell-to-cell transmission and that ApoE knockdown from donor cells causes less-efficient cell-to-cell transmission. Thus, this work indicates that the complete HCV assembly machinery is required for HCV cell-to-cell transmission. At last, this work presents an optimized viral infection-activated split-intein-mediated reporter system for easy live-cell monitoring of HCV infection.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.